We propose to study the biological and chemical induction of differentiation in human colon carcinoma cells. The primary objective of this differentiation-induction, or maturation-induction, study is to cause the revertance in culture of colon cancer cells to more normal or benign cell types. A specific aim is the reduction of the tumorigenicity of these cells; the tumor potential of inducer-treated versus untreated tumor cells will be assayed using nude mice. A secondary objective will be to improve methods for the establishment of human normal colon and colon carcinoma cell lines, and then to study our established lines. Our lines will be characterized by the determination of specific ultrastructural and antigenic markers. These markers along with the tumorigenicity parameter will provide the basis for evaluation of the success of our differentiation-induction experiments.